nervous system
N |
• thalamocortical projections are tight bundles in the internal capsule and fascicle arrays in the striatum, similar to wild-type brains
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• in postnatal brains at P0, P1, P4 and P7, misrouted axons and aberrant fasciculation are observed in the white matter, striatum, and corticostriatal junction
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• most thalamocortical axons (TCAs) display a normal innervation path and targeting, but numerous TCAs are misrouted and extend ventrolaterally in the pallial-subpallial boundary (PSPB) before turning dorsomedially into the cortical plate to join with other TCAs
• most corticothalamic axons (CTAs) show normal innervation paths and targeting, but numerous abnormally large CTA fascicles are observed close to the pallial-subpallial boundary at E16.5
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• mutants have more thalamocortical axon (TCA) fascicles (greater than 50%) with diameters > 14 um (some are >25 um, while control brains have very few fascicles that are > 20 um in diameter with 50% having diameters < 8 um at E16.5
• density of fascicles is significantly lower than in controls (3.8 per 10000 sq. um); mutants have fewer but larger TCA fascicles in the pallial-subpallial boundary area
• in postnatal mice (p0-P7), abnormally large TCA fascicles are observed; no correction of the developmental phenotype is observed with age
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• under high frequency stimulation, long term potentiation is enhanced
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• long term depression of inhibitory postsynaptic currents is absent
• however, long term depression under low frequency stimulation is normal
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• suppression of GABA-mediated synaptic transmission does not increase paired-pulse facilitation as in wild-type mice
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behavior/neurological
N |
• mice exhibit normal foot-shock-induced behavioral sensitization, unconditioned freezing to tone, anxiety-related behaviors, and locomotion
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• while mice perform normally in a cued conditioning assays, they fail to extinguish the freezing response over time unlike wild-type mice
• mice fail to exhibit extinction of averse memories as in wild-type mice
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• mice exhibit reduced exploratory behavior in an elevated plus maze compared to wild-type mice
• however, locomotion in an open field test is normal
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cellular
• mutants have more thalamocortical axon (TCA) fascicles (greater than 50%) with diameters > 14 um (some are >25 um, while control brains have very few fascicles that are > 20 um in diameter with 50% having diameters < 8 um at E16.5
• density of fascicles is significantly lower than in controls (3.8 per 10000 sq. um); mutants have fewer but larger TCA fascicles in the pallial-subpallial boundary area
• in postnatal mice (p0-P7), abnormally large TCA fascicles are observed; no correction of the developmental phenotype is observed with age
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